“Patologia neoplastica borderline dellamammella"

Anna SapinoDepartment of Medical Sciences

University of Torino (Italy)

B3 Lesion of uncertain malignant potential

This category mainly consists of lesions which may provide benign histology on CB, but

either are known to •show heterogeneity or

•to have an increased risk (albeit low) of associated

malignancy.

• columnar cell lesions• atypical ductal hyperplasia • lobular neoplasia (atypical lobular hyperplasia

and lobular carcinoma in situ)

• papillary lesions • radial scars

Nonmalignant lesions in breast core needle biopsies:

to excise or not to excise?JacobsT, Connolly J, Schnitt,SJ

Am J Surg Pathol 26(9): 1095–1110, 2002

• columnar cell lesions• atypical ductal hyperplasia • lobular neoplasia (atypical lobular

hyperplasia and lobular carcinoma in situ)

• papillary lesions • radial scars

Nonmalignant lesions in breast core needle biopsies:

to excise or not to excise?JacobsT, Connolly J, Schnitt,SJ

Am J Surg Pathol 26(9): 1095–1110, 2002

sedi di originesedi di origine

Columnar alteration of lobules. This lesion is characterized by an enlarged lobule with slightly dilatedacini (A). The acini are lined by a single layer of columnar epithelial cells with elongated nuclei (B). Apical snout

Am J Surg Pathol. 1998 Dec;22(12):1521-7.

Columnar cell change

Advances in AnatomicPathology 10: 113–124 (2003)

Columnar cell hyperplasia

Bonser, Dossett and Jull. 1961 Columnar metaplasia

Azzopardi 1979. Blunt duct adenosis

•BDA with response of the specific stroma (organoid) •Non-organoid BDA•Microcystic BDA

Advances in Anatomic PathologyVol. 10, No. 3, pp. 113–124 (2003)

Columnar cell lesion with atypia/flatepitheliel atypia/FEA

Flat epithelial atypia

FEADIN1A

FEA/DIN1A

ADH/DIN1B

DCIS/DIN1C

The The ‘‘‘‘RosenRosen TriadTriad’’’’: : TubularTubular Carcinoma, Carcinoma, LobularLobular Carcinoma In Situ, and Carcinoma In Situ, and ColumnarColumnar Cell Cell

LesionsLesions

Suzanne M. Brandt, MD, Gloria Q. Young, MD, and Syed A. Hoda, MD

Adv Anat Pathol. 2008 May;15(3):140-6

1. High ER expresion2. HER2 negative3. Low proliferation

FEA/DIN1a CLIS/LIN DCIS/DIN1c

IMMUNOPHENOTYPE

ER ER ERER

ADH/DIN1b

Laboratory Investigation (2008) 88, 938–948

J Clin Oncol 27:5138-5143. 2009

Estrogen-progestagen menopausal hormone therapy (EP-MHT) and breastcancer risk varies according to the delay between menopause onset and treatment initiation. When initiated close to menopause, even short

durations of use are associated with an increased breast cancer risk.

HRT is more likely to be a tumor promoter thana de novo-inducer of breast cancers

Maturitas 65 (2010) 183–189

FEA/DIN1A

DIN1C

Am J Surg Pathol 2007;31:417–426

Continuum biologico

DIN

1aD

IN1b

DIN

1c

Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-

analysis. Lancet Oncol. 2006 Nov;7(11):910-8

1.031.224 postmenopausal women recruited in 1996-2001

14 102 breast cancers

RR in current users compared with never users of hormone therapy

INVASIVE CARCINOMAlobular 2.25 (95% CI 2.00-2.52)mixed ductal-lobular 2.13 (95% CI 1.68-2.70) tubular cancers 2.66 (95% CI 2.16-3.28)ductal 1.63 (95% CI 1.55-1.72) mucinous cancers 1.58 (95% CI 1.08-2.31) medullary cancer was not increased 0.74 (95% CI 0.43-1.28)

IN SITU CARCINOMAlobular carcinoma in situ 2.82 (95% CI 1.72-4.63)Ductal carcinoma in situ 1.56 (95% CI 1.38-1.75)

(p<0.0001)

Modern Pathology (2009) 1–8

Women should be advised of the possible hormone dependency of CCLs.

• Page’s view that the cellular changes of DCIS are present but occupy less than 2 separate duct spaces is widely accepted

• Others use a 2 mm cut-off; a lesion less than 2 mm in maximum dimension being classified as ADH and a larger area as DCIS (Tavassoli 1992).

• Others mention the involvement of a single TDLU. These criteria recognise essentially the same lesions. In essence, ADH is usually small and focal, measuring less than 2 to 3 mm. Larger foci are accepted if associated with a radial scar/complex sclerosing lesion or a papilloma.

European Guidelines for quality assurance in breast cancer screening and diagnosis Fourth edition- Supplement 2012

ADH

ADH/Low grade DCIS (size)

• ADH is formed from a uniform population of small or medium-sized round, cuboidal or polygonal hyperchromatic cells, which are regularly arranged.

• The nuclei are evenly distributed and may form a rosette-like pattern. Single small nucleoli only are present. Mitoses, particularly abnormal forms, are infrequently seen.

• Geometric spaces are noted and, in the cribriform type, the cells are arranged at right angles to the bridges formed. Micropapillary ADH is also recognised and a solid pattern may very rarely be seen.

• Small foci of necrosis may rarely be identified in ADH and do not indicate that the process should be classified as DCIS

ADH/Low grade DCIS (size)

http://www.breastpathology.info/Benign%20proliferative%20disease.html

•Aspetto a corrente

•Fenestrature periferiche

•Variabilitànucleare

•No mitosi

Accumulo cellulare senza proliferazione

Hum Pathol. 2006;37:787-93.

ADH is a clonal process, uniform phenotype and immunophenotype

FEA/DIN1A

DIN1C

LIN

RESECTION MARGIN

LIN1/2DIN1ADIN1BDIN1C

CLIS FEAADHDCIS low grade

Lesione stellata Distorsione architetturale

BLACK STAR

1- deposito di connettivoFIBRO-ELASTICO “cicatrice”2- rari dotti con epitelio e mioepitelio inglobati

3- iperplasia o carcinomain situ intorno alla cicatrice

CICATRICE SCLERO-ELASTOTICA

WHITE STAR

CARCINOMA TUBULARE

CK5/6

CE

CT

CT

ADENOSI SCLEROSANTE

Usually incidental but may be a mass lesionOften associated calcs -picked up on screeningMay be confused with cancers histologicallyLow power view critical to make correct diagnosis.....

The edge of a focus may be apparently infiltrative but less so than many low grade carcinomasAt high power the glands are very crowded and may be cytologically atypicalAround some glands at least you should be able to see a compressed myoepithelial layerImmunostaining shows an intact myoepithelial layer e.g. with CK 5/6

Atypical apocrine sclerosing lesion

Sclerosing adenosis lesion with superimposed apocrine metaplasiaAtypia may be moderately severe - distinction from apocrine DCIS (with lobular cancerisation) may be difficultImmunostaining will demonstrate an intact myoepithelial layer and basement membraneFollow up of patients showed no greater cancer risk than other atypical lesions

well-defined margins and a surrounding lucent ‘‘halo’

Clinical Radiology (2008) 63, 1265e1273

well-defined, ovoid mass, predominantly solidappearance, but with a cystic component markedposterior acoustic enhancement

Background: debris +; histiocytes +; blood +;

Cellularity: +++ (poor if sclerotic); Large 3D sheets: ++

fibroadenoma papillary lesion

Large 3D sheets , origami like folding Fibrovascular cores: ++; Cell clusters: ++Single cells: ++; Myoepithelial cells: +Histiocytes:++

Lesione sclerosante complessa

•Aree Solide

(iperplasia duttale atipica)

Virchows Arch (2003) 443:609

CK5 CK14

GCDFP-15ER

Virchows Arch. 2007;450:539

Papilloma atipico

Cribriform pattern (iperplasia duttale atipica)

Carcinoma Papillare in situ

Singola fila di cellule epiteliali

Lesione papillare con LIN (13%)

E-cadherin

Solitary, circumscribed tumor, arborizing papillary fronds surrounded by a fibrotic rim.

Intracystic papillary carcinomaAm J Surg Pathol 2006;30:1002–1007

Solid or cribriform pattern of growth of monomorphic epithelial cells.

Intracystic Papillary Carcinomas of the Breast: A Reevaluation Using a Panel of Myoepithelial Cell Markers

Laura C. Collins, et al.

Am J Surg Pathol 2006;30:1002–1007

‘‘Encapsulated Papillary Carcinoma’’circumscribed nodules of papillary carcinoma

surrounded by a fibrous capsule in which a peripheral layer of

MEC is not identifiable.

p63 CD10 ck5/6

FNA: Carcinoma papillare intracistico/incapsulat

Expansive lesions, forming solid sheets and festoons, lined by delicate fibro-vascular stroma.

aged women

Solid Papillary Carcinoma

CgA

J Clin Pathol 2008;61:945–949

How important is the differential diagnosis for patient management?

Am J Surg Pathol 2006;30:1002–1007

Available outcome data indicate that they have an excellent prognosis with adequate localtherapy alone.We believe it is most prudent to continue to manage patients with these lesions as they are currently managed (ie, similar to patients with DCIS) and to avoid categorization of such lesions as frankly invasive papillary carcinomas.

Intracystic/encapsulated papillary carcinoma

Cancer 2008;113:916–20

this overall survival rate may be influenced by the older age of patients (mean age 69.5 years-range27 years-99 years)and consequent comorbidities

It is obtained by adjusting observedsurvival for the normal life expectancyof the general population of the sameage, the relative survival rate is an estimate of the chance of surviving the effects of cancer.

The addition of radiation to the treatment of patients did not change the incidence of localrecurrence or likelihood of death compared with those who did not receive radiation

Am J Surg. 2002;184:364-368

There has been no clear indication for adjuvantendocrine therapy, even among patients with estrogenreceptor–positive tumors.Furthermore, the addition of hormonal treatment does not appear to have impacted outcome.

Br J Surg. 1999;86:1274.

SPC has an indolentbehavior.

Lymph node and distantmetastases are uncommon and generallylimited to cases with (conventional) invasive components.

Nassar H et al. Am J Surg Pathol 2006;30:501–507

Clinicopathologic Analysis of Solid Papillary Carcinoma ofthe Breast and Associated Invasive Carcinomas